(California Court of Appeal) - Affirmed. Plaintiff sued for negligence and premises liability for an assault that injured him in the Defendant's parking lot. The trial court found that Plaintiff had not met his burden of showing foreseeability of violent criminal assaults. Therefore, Defendant did not have a legal duty to implement additional security measures to prevent possible third-party conduct.

CC Is Now Set To Unleash His Highly Anticipated New Single “I SEE LOVE” On All Digital Services August 9, 2019.

The surviving members of Soundgarden have filed a counter-lawsuit

His vacation hair is all wrong.

Nearly everyone on Earth is familiar with corn. Literally. Around the world, each person eats an average of 70 pounds of the grain each year, with even more grown for animal feed and biofuel.

Instant Pot Cranberry Cornbread Bites shaped like Christmas Jingle Bells, pair up for the perfect bite of sweet and tart spiced cranberries.

craving more? check out TasteSpotting

Cornel West and Tavis Smiley criticize President Barack Obama for being to the right of even President Richard Nixon. Continue reading →

This Thursday (4/9), eighteen authors (including yours truly!) will be doing live readings to celebrate International Unicorn Day!!! At 10:30am ET, I'll be on Facebook Live on my author page here: https://www.facebook.com/sarahbethdurst

And I may be wearing a unicorn onesie... 

1. ABC’s Four Corners to investigate NRL’s financial woes  Daily Telegraph
2. Report: Rugby league players to be forced to decide between state and Test level footy  Wide World of Sports
3. NRL 2020: Peter V’landys set to cut $50m from League Central  Courier Mail
4. How a farm system could help the NRL expand  The Roar
5. View Full coverage on Google News

Support this Podcast by visiting Jim’s Patreon Page   David Collum is the Betty R. Miller Professor of Chemistry at Cornell University. He is the intellectual utility infielder of internet commentary, covering all the bases: culture, politics, finance, science, and technology, with often surprising views on the the predicaments of our time. Here we attempt to more »

The post KunstlerCast 326 — Confab with David Collum of Cornell U about Corona Virus, Markets Gone Wild, and Politics appeared first on Kunstler.

Hello everyone hope you're all okOur first night of hostel living was interesting quite a noisy and interrupted night so didn't get a lot of sleep no chance of getting over the jet lag there I really don't understand people who have showers at 4am

Glenn, a former boxer and owner of popular Times Square bar Jimmy's Corner, died of coronavirus early Thursday morning at 89.

Chris Cornell’s widow is firing back at her husband’s Soundgarden bandmates, calling the lawsuit they filed against her Wednesday an attempt to “browbeat” her into giving up “copyrighted works.”

USC to hire Donte Williams to be its cornerbacks coach and defensive passing game coordinator, according to a person familiar with the decision.

Chris Cornell’s widow is firing back at her husband’s Soundgarden bandmates, calling the lawsuit they filed against her Wednesday an attempt to “browbeat” her into giving up “copyrighted works.”

Glenn, a former boxer and owner of popular Times Square bar Jimmy's Corner, died of coronavirus early Thursday morning at 89.

Chris Cornell’s widow is firing back at her husband’s Soundgarden bandmates, calling the lawsuit they filed against her Wednesday an attempt to “browbeat” her into giving up “copyrighted works.”

Glenn, a former boxer and owner of popular Times Square bar Jimmy's Corner, died of coronavirus early Thursday morning at 89.

Rishi Reddi's "Passage West" plumbs an important story of Indian immigrant farmers, but isn't quite up to the task as fiction

Lionsgate and special guests stream familiar titles, including "Hunger Games," "Dirty Dancing" and "John Wick," to benefit furloughed movie theater workers.

The Virtual Grand National replaces the real-life National this afternoon with ITV providing life coverage of a lifelike simulation to substitute for the cancelled regular race. Express Sport brings you live updates with an animated Tiger Roll the favourite for victory.

Potters Corner triumphed at the Virtual Grand National with an explosive finish in a boost to the NHS.

You can’t say that you have travelled until you visit all the continents of the world. If you’re a hardcore traveler, it’s best to explore not only one side of the globe, but all parts...

The post Travel to Different Corners of the World appeared first on Geeky Traveller.

General Mills recalls Green Giant Original Sweetcorn because some seams may be faulty due to a packaging fault, which could make this product unsafe to eat.

ANT MIDDLETON'S wife, Emilie Middleton, reportedly "misjudged a corner" and crashed the SAS star's 200K car while on the way to the shops during the coronavirus lockdown.

After nearly 100 years, the northern Indiana resort and amusement park closes. The park near Monticello was originally named Ideal Beach.

Tiawan Mullen, who will be a sophomore, has been throwing questions at IU football cornerbacks coach Brandon Shelby all spring

The startup anti-patterns section of my blog summarizes the repeatable ways startups waste time & money and, often, fail. Learning from startup failure is valuable because there are many more examples of failures that successes. (Anti-)Patterns become more noticeable and … Continue reading →

How poverty and economic inequality are threatening an entire generation of African Americans.

“Clearly my sister’s paycheck is more important than the world her three adopted kids will inherit,” Curtis Ingraham wrote on Twitter.

The Amateur Traveler talks to Erik Smith again about his trip to the Four Corners area in the American southwest. Four Corners is the spot where 4 U.S. states meet: Utah, Arizona, New Mexico and Colorado. While the Four Corners spot itself is just a photo op (an probably at the wrong place), the area around it contains some amazing scenery and historic sites. Erik gives us a state by state break down of the area. He tells us about National Parks nearby like Arches Canyonlands, Hovenweep, Moab, Canyon de Chelly, Rainbow Bridge, Mesa Verde , Chaco Culture, Black Canyon of the Gunnison, Petrified Forest and Aztec Ruins. The area also boats the spectacular and iconic scenery of Monument Valley and a stretch of road known as the “Million Dollar Highway”. It has many Native American sites including those like Canyon de Chelly run jointly by the Navajo nation and the U.S.

The Gothamist is reporting the sad news that Gem Spa, the iconic NY corner store that has been a fixture at St. Marks Place and Second Avenue for around 100 years is being forced to shutter its doors and windows for the last time. The Spa has been struggling to keep up with increasing rent prices and COVID-19 has apparently proven to be the final nail in its coffin.

"It’s where Robert Mapplethorpe bought Patti Smith an egg cream on the day they met. It’s on the back cover of the New York Dolls’ 1973 debut (and where, according to lore, Johnny Thunders and others went for post-heroin sugar fixes between sets at CBGB). Before that, it was where Abbie Hoffman gathered Yippies to rain money on the New York Stock Exchange. It’s where Allen Ginsberg, Ted Berrigan, and other neighborhood poets went to pick up the Sunday New York Times on Saturday nights (and which was inevitably commemorated in their poems)."

Read the rest.

Image: Alex Lozupone, CC BY-SA 4.0 Read the rest

On May 16, 2010, at 10:02 AM, "Xx" wrote:

You mentioned you gave a talk at Rutgers about future proofing your passion. Is this available as a podcast? I'd love to listen!

This poor kid emailed me to ask a really simple question. And I went and saddled him with the world's most circuitously long-winded answer. Surprise, surprise.

Hey, Xx,

Thanks for the note, man. No I'm sorry its not up as audio AFAIK.

FWIW, it's a talk I'm asked to do more often lately so I wouldn't be surprised if it turns up sooner or later.

Since you were kind enough to ask, the talk—which comes out super different each time I do it— consists of a discursive mishmash of advice I wish I'd had the ears to hear in the year or five after graduating from college: primarily, that we never end up anywhere near where we'd expected, and that most of us would have been a lot happier a lot faster if we'd realized that we were often obsessing over the wrong things—starting with how much the world should care about our major. ("Liberal Arts," with a concentration in [ugh] "Cultural Studies," thanks.)

The talk started as a way to encourage students to learn enough about what they care about that any temporary derails and side roads wouldn't scare their horses too badly. But, today, I see it as something a lot bigger that's demonstrably useful to anyone who hopes to survive, evolve, and thrive in this insane world.

A handful of bits I'm (obviously) still synthesizing into something notionally cohesive:

My Kingdom for Some Context!

For myself, I wish I'd known the value of developing early expertise in interesting new skills around emerging technologies (rather than just iteratively pseudo-honing the 202-level skills I thought I "understood"). Alongside that, I wish I'd learned to embrace the non-douchier aspects of building awesome human relationships (as against "networking" in the service of landing some straight job that, as with most hungry young people, locked me into a carpeted prison of monkey work at the worst time possible).

Also how I wish I'd paid more attention to events, contexts, relationships, and change that were happening outside my immediate world —rather than becoming, say, the undisputed master of fretting about status, salary, and whether I was "a success" who had "arrived".

Hint: I was not a "success," and I had not, by any stretch, "arrived."

To my mind, "success" in the real world is much more the equivalent of achieving a new personal best; it's not about whether you won the "Springtime in Springfield SunnyD®/Q105™ 5k FunRun for Entitilitus," and got a little ribbon with a gold crest on it.

Truly, pretty much anyone who feels they've "arrived" anyplace is about to learn a) how much more they could be doing outside the narrowness of an often superficial ambition and b) the surprising number of things they had to give away through the opportunity costs and trade-offs that lead up to every theoretical milestone. It's a real goddamned thistle, and it's more than a little depressing.

Do You Still Really Want to be a Fireman?

[N.B.: I really hope you're taking bathroom breaks here, Xx]

Related, I think this is about how being an adult is not only unbelievably complicated in ways that you can't begin to imagine—that it's frequently defined by impossible decisions and non-stop layers of "hypocrisy"—but that there's an invisible but entirely real risk to doggedly chasing the theoretically laudable notion of "following your dream." Especially if it's a dream you first had while sleeping on Star Wars sheets in a racecar bed.

Not because it's a bad idea to want things or to have ambitions. Quite the opposite. More because, for a lot of us, the "dreams" of youth turn out to be half-finished blueprints for wax wings. And not particularly flattering ones at that.

By starting adult life with an autistically explicit "goal" that's never been tested against any kind of real-world experience or reality-in-context, we can paradoxically miss a thousand more useful, lucrative, or organic opportunities that just…what?…pop up. Often these are one-time chances to do amazing and even unique things—opportunities that many of us continue to reject out of hand because it's "not what we do."

It took me a full decade to learn to embrace the unfamiliar gifts that kismet loves to deliver on our busiest and most stressful days, and which gifts might (maybe/maybe not) even end up bringing the real-life, non-racecar-bed, now me a big step closer to something that's 1000 times more interesting than a hollow, ten-year-old caricature of "what I wanna be when I grow up."

Finding Your "Old Butcher"

Also related, it strikes me that the indisputable wealth of information and options that are provided by the web often comes with a harrowing hidden tradeoff. While we can certainly learn a lot on our own and become (what feels like) an instant expert on any topic in an afternoon, we usually do so in the absence of a mentor and outside the context of applying expertise to solve actual problems. In my opinion, a cadet should have to survive more than a few Kobayashi Maru scenarios before he gets to declare himself, "Captain."

Call it a guru, a wizard, an old butcher, or what have you, the mad echo chamber of a young mind often benefits from the dampening influence of an experienced grownup who can help you understand things that raw data, wikipedia entries, and lists of tips and tricks can't and wont ever do.

We benefit from a hand on the back and a gentle voice, reminding us:

• "Try not to obsess over implementation until you really understand the problem," or
• "Worry more about relationships than org charts or follower counts," or
• "Don't quit looking after you've found that first data point," or—my favorite—
• "Spend less time fantasizing about 'success' and way more time making really cool mistakes."

Conversely, though, I think this means that everything we think we know, as well as all the fancy advice that gets thrown around—absolutely including the material you're reading now—is the product of what one person knows and what another person has the ears to hear. For us. For now. For who really knows what. But it is a transaction that takes place in a very specific time and within the bounds of a set of "known" "facts." So, fair warning, doing your own due diligence never hurts.

What's Almost Not Impossible?

[N.B.: I swear to God this ends at some point, Xx]

One big pattern for "future-proofing" your passion? Keep your eyes open and your heart even "opener." And, be more than simply tolerant of the notion of change—sure, take it as read that nothing is ever fixed in place for more than a little while.

But, to the extent that your sanity can bear it, always keep an eye on the corners, the edges, and especially learn to watch for those infinitesimally tiny figures starting to shuffle around near the horizon. Because a lot of the things that seem ridiculously small and inconsequential right now will eventually cast a shadow that people will be chasing for decades. It's just that we're never sure which tiny figure that will turn out to be.

So, yeah. It really is true that no one but you cares about your major. But, trust me: everybody is interested in the person who repeatedly notices the things that are about to stop being impossible.

Be the curious one who soaks in all that "irrelevant" stuff. And, even as you stay heads-down on the "now" projects that keep the lights on, remember that the guy who invented those lights made hundreds of "failed" lightbulbs before fundamentally upending the way we think about time, family, industry, and the role of technology in how we live and work. But, yes, first he "failed" a lot a lot at something which more than a few of his contemporaries thought was pointless in the first place.

Ask: What's out there right now that's about to stop being impossible? Where will it happen first? Who will (most loudly and erroneously) declare it's total bullshit? Who will mostly get it right—but possibly too early? Who will figure out what it means to our grandkids? Who will figure out how to put it in everyone's front pocket for a quarter?

Y'know who? I'll tell you who: practically anybody BUT that guy in the racecar bed who wants to talk about his major.

Important: Merlin's Advice is Only Future-Proof to 10 Meters

A few years back, most watch manufacturers decided to come clean and stop categorically declaring that their timepieces were "waterproof." Instead, today, the more credible vendors admit their product is merely "water-resistant"—and, even then, they'll only guarantee the underwater functionality at so many meters, and for so long, and under thus and such conditions.

Truthfully, the same applies here. Nothing can actually "future-proof" anything. Anyone who claims to know the future is either a madman, a charlatan, or, often as not, both.

Thing is, regardless of the passions (or goals or values or priorities or whatever) that we hope to protect or defend, we'd all do well to remember that it is still ultimately OUR passion that's at stake.

That means we're the only one responsible for seeing that its functional components survive and adapt in a world in which each one of us has just north of zero control.

If we embrace the fact that no one can or should ever care about the health of our passions as much as we do, the practical decisions that help ensure Our Good Thing stays alive can become as "simple" as a handful of proven patterns—work hard, stay awake, fail well, hang with smart people, shed bullshit, say "maybe," focus on action, and always always commit yourself to a bracing daily mixture of all the courage, honesty, and information you need to do something awesome—discover whatever it'll take to keep your nose on the side of the ocean where the fresh air lives. This is huge.

Anything else? Yeah. Drink lots of water, play with your kid every chance you get, and quit Facebook today. No, really, do it.

Thanks again for the note, Xx, and sorry for the novella. I'll ping you if the audio ever turns up. Til then, forget your major, and break a leg!

yr internet pal,
/m

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K₂ subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.

Alexander J. Rasmussen
Proc. Amer. Math. Soc. 148 (2020), 2345-2357.
Abstract, references and article information

The 'unicorn letter', sent by some of the best-funded private technology companies in the country, asks the chancellor to form an urgent taskforce to give them access to government-backed lending schemes during the pandemic

Dong-Jae Jun
May 1, 2020; 61:746-757
Research Articles

Momoko Kawana
Apr 7, 2020; 0:jlr.RA120000671v1-jlr.RA120000671
Research Articles

Ceramides are the predominant lipids in the stratum corneum (SC) and are crucial components for normal skin barrier function. Although the composition of various ceramide classes in the human SC has been reported, that in mice is still unknown, despite mice being widely used as animal models of skin barrier function. Here, we performed LC–MS/MS analyses using recently available ceramide class standards to measure 25 classes of free ceramides and 5 classes of protein-bound ceramides from the human and mouse SC. Phytosphingosine-type ceramides (P-ceramides) and 6-hydroxy sphingosine-type ceramides (H-ceramides), which both contain an additional hydroxyl group, were abundant in human SC (35% and 45% of total ceramides, respectively). In contrast, in mice, P-ceramides and H-ceramides were present at ~1% and undetectable levels, respectively, and sphingosine-type ceramides accounted for ~90%. In humans, ceramides containing α-hydroxy FA were abundant, whereas ceramides containing β-hydroxy FA (B-ceramides) or -hydroxy FA were abundant in mice. The hydroxylated β-carbon in B-ceramides was in the (R)-configuration. Genetic knockout of β-hydroxy acyl-CoA dehydratases in HAP1 cells increased B-ceramide levels, suggesting that β-hydroxy acyl-CoA, an FA-elongation cycle intermediate in the endoplasmic reticulum, is a substrate for B-ceramide synthesis. We anticipate that our methods and findings will help to elucidate the role of each ceramide class in skin barrier formation and in the pathogenesis of skin disorders.

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K₂ subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.

The purpose of this study was to investigate the protective role of Peroxisome Proliferator-Activated Receptor-alpha (PPARα) against diabetic keratopathy and corneal neuropathy. Corneal samples were obtained from diabetic and non-diabetic human donors. Streptozotocin-induced diabetic rats and mice were orally treated with PPARα agonist fenofibrate. As shown by immunohistochemistry and Western blotting, PPARα was down-regulated in the corneas of diabetic humans and rats. Immunostaining of β-III tubulin demonstrated that corneal nerve fiber metrics were decreased significantly in diabetic rats and mice, which was partially prevented by fenofibrate treatment. As evaluated using a Cochet-Bonnet aesthesiometer, corneal sensitivity was significantly decreased in diabetic mice, which was prevented by fenofibrate. PPARα^-/- mice displayed progressive decreases in the corneal nerve fiber density. Consistently, corneal sensitivity was decreased in PPARα^-/- mice relative to wild-type mice by nine months of age. Diabetic mice showed increased incidence of spontaneous corneal epithelial lesion, which was prevented by fenofibrate while exacerbated by PPARα knockout. Western blot analysis revealed significantly altered neurotrophic factor levels in diabetic rat corneas, which were partially restored by fenofibrate treatment. These results indicate that PPARα protects corneal nerve from degeneration induced by diabetes, and PPARα agonists have therapeutic potential in the treatment of diabetic keratopathy.

Diabetic Keratopathy, a sight-threatening corneal disease, comprises several symptomatic conditions including delayed epithelial wound healing, recurrent erosions, and sensory nerve (SN) neuropathy. We investigated the role of neuropeptides in mediating corneal wound healing, including epithelial wound closure and SN regeneration. Denervation by Resiniferatoxin severely impaired corneal wound healing and markedly up-regulated pro-inflammatory gene expression. Exogenous neuropeptides CGRP, SP, and VIP partially reversed Resiniferatoxin’s effects, with VIP specifically inducing IL-10 expression. Hence, we focused on VIP and observed that wounding induced VIP and VIPR1 expression in normal (NL), but not diabetic (DM) mouse corneas. Targeting VIPR1 in NL corneas attenuated corneal wound healing, dampened wound-induced expression of neurotrophic factors, and exacerbated inflammatory responses while exogenous VIP had the opposite effects in DM corneas. Remarkably, wounding and diabetes also affected the expression of Sonic Hedgehog (SHH) in a VIP-dependent manner. Downregulating SHH expression in NL corneas decreased, while exogenous SHH in DM corneas increased the rates of corneal wound healing. Furthermore, inhibition of SHH signaling dampened VIP-promoted corneal wound healing. We conclude that VIP regulates epithelial wound healing, inflammatory response, and nerve regeneration in the corneas in a SHH-dependent manner, suggesting a therapeutic potential for these molecules in treating diabetic keratopathy.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor widely expressed in mammalian tissues, and it exerts critical protective effects on neurons and other cell types in various disease models, such as those for diabetes. However, to date, the expression and roles of MANF in the cornea, with or without diabetic keratopathy (DK), remain unclear. Here, we demonstrate that MANF is abundantly expressed in normal corneal epithelial cells; however, MANF expression was significantly reduced in both unwounded and wounded corneal epithelium in streptozotocin-induced type 1 diabetic C57BL/6 mice. Recombinant human MANF significantly promoted normal and diabetic corneal epithelial wound healing and nerve regeneration. Furthermore, MANF inhibited hyperglycemia-induced endoplasmic reticulum (ER) stress and ER stress–mediated apoptosis. Attenuation of ER stress with 4-phenylbutyric acid (4-PBA) also ameliorated corneal epithelial closure and nerve regeneration. However, the beneficial effects of MANF and 4-PBA were abolished by an Akt inhibitor and Akt-specific small interfering RNA (siRNA). Finally, we reveal that the subconjunctival injection of MANF-specific siRNA prevents corneal epithelial wound healing and nerve regeneration. Our results provide important evidence that hyperglycemia-suppressed MANF expression may contribute to delayed corneal epithelial wound healing and impaired nerve regeneration by increasing ER stress, and MANF may be a useful therapeutic modality for treating DK.

Dentists’ comfort levels and perceived roles in discussing and administering the human papillomavirus vaccine appear to vary, according to the results of an American Dental Association Clinical Evaluators Panel survey published in The Journal of the American Dental Association.

OBJECTIVE

Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables.